TMPRSS3 (transmembrane protease, serine 3) is a member of Ⅱ transmembrane serine proteases (TTSPs), and like the other members of this family, it contains typical domains including a serine protease domain, a transmembrane domain, a LDL receptor-like domain (LDLRA), and a scavenger receptor cysteine-rich domain (SRCR). Four alternative protein isoforms have been described, and isoform A is thought to be primary isoform which is expressed in many tissues, especially in the cochlea. TMPRSS3 protein is primarily localized in the endoplasmic reticulum membranes where it may be anchored by its transmembrane domain. TMPRSS3 is mutated in non-syndromic autosomal recessive deafness (DFNB8/10). Therefore TMPRSS3 is thought to be involved in the development and maintenance of the inner ear, and isoform D may be proposed as a novel diagnostic marker in ovarian carcinoma. TMPRSS3 protein is the first protease which mutation could lead to deafness. These data indicate that important signaling pathways in the inner ear are controlled by proteolytic cleavage. However, it is not clear about TMPRSS3 substrates and its function. The epithelial amiloride-sensitive sodium channel (ENaC) which is regulated by membrane-bound channel activating serine proteases (CAPs), a member of TTSPs, may be a potential substrate of TMPRSS3, but this hypothesis is still to be verified in vivo. With the development of protease research and the application of protease proteomics, substrate degradomes of a protease may therefore represent an important tool for the research of TMPRSS3 function and its molecular mechanism.

Aim To observe the optimal temperature and optimal pH of uricase-catalase liposomes(UCALP) and free uricase(UAE), and study the abilities of UCALP to reduce uric acid and hydrogen peroxide in mice with hyperuricemia.Methods UCALP were prepared by reverse phase evaporation, optimal temperature and optimal pH of UCALP and UAE were determined, respectively.Mouse model of hyperuricemia was established by intraperitoneally injection of uric acid, and the model mice were intravenously injected UCALP and UAE, respectively, then the serum concentration of uric acid and hydrogen peroxide in mice at different time points were measured by the assay kits, respectively.Results Optimal temperature of UCALP and UAE was 40℃, and optimal pH was 8.0 and 8.5, respectively.UCALP could more significantly lower uric acid level of hyperuricemia mice than that of UAE, and the concentration of hydrogen peroxide in UCALP group was lower than in UAE group.Conclusion UCALP can effectively decrease the level of uric acid and control the level of hydrogen peroxide in mice with hyperuricemia.

No-reflow phenomenon after reperfusion treatment of acute myocardial infarction (AMI) is becoming more recognized today. The effective treatment for no-reflow has not been reported.

Objectives To establish the two-dimensional electrophoresis(2-DE)profile of cell. Secreted proteins.Difierential expression profiling of fibroblast cell secreted proteins between nasopharyngeal carcinoma and normal nasopharyngeal tissue was analyzed.Methods Five tissue specimens each from patients with nasopharyngeal carcinoma and nasal polyp were collected individually.Fibroblast eells from above-mentioned tissue were cultured in serum-free medium,and cell-secreted proteins from the cultured medium were harvested by uhrafihration concentration and desalination.Samples were analyzed by 2-DE,and the differentially expressed proteins were analyzed and identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry.Galectin-1 wa8 analyzed by EUSA test.Results 2-DE diagram of fibroblast cell-secreted proteins Was constructed.1 8 protein spots displayed quantitative changes in expression,and 11 protein spots among them were identified by mass speetrometrv.3 proteins including cystatin C,complement subcomponent C1S precursor,heterogeneous nuclear ribonueleoprotein A1 were down-regulated in the cultured medium of nasopharyngeal carcinoma associated fibroblast cells(CAFs). Nevertheless,the rest cell-secreted proteins including galectin-1,14-3-3 protein sigma,eathepsin L and etc,were up-regulated.Meanwhile,the expression of galectin-1 in the cultured medium was also analyzed and Its results were compared between CAFs and the normal fibroblast cells by ELISA.There Was statistical significance difference between them,and galectin-1 was up-regulated in the cIlltured medium of CAFs.Conclusions The changes of fibroblast cell-secreted proteins during nasopharyngeal carcinogenesi8 are analyzed by 2-DE analysis.The variation of pattern of secreted proteins is involved in signal transduction,protein synthesis,degradation and other pathways.CAFs may regulate tumor microenvironment by the abeve-mentioned pathways,and influence nasopharyngeal carcinogenesis,progress,invasion and metastasis.This study provided experimental basis for the eell secreted proteomics studv in future.

Objective:To investigate the clinical features and feasibility genetic diagnosis in a hereditary hemorrhagic telangiectasia (HHT) family,and to explore the application of gene mutation testing in HHT diagnosis.Methods:Medical histories and clinical features of a family were analyzed to diagnose HHT patients and suspected individuals according to the clinical diagnostic criteria.Sequence analysis of endoglin (ENG) and activin A receptor like type 1 (ACVRL1) gene in the proband was performed with PCR and Sanger sequencing technology.After the possible pathogenic mutation was identified in the proband,the specific mutation was detected in the suspected individuals and part of other family members.Then the genetic diagnoses were concluded.Results:There were 5 family members in 4 generations manifested with epistaxis.According to the clinical diagnosis criteria,the proband with epistaxis,mucocutaneous telangiectases,visceral arteriovenous malformation and family history was diagnosed as HHT;while 2 survival family members with epistaxis and family history were suspected individuals.A substitution mutation in the 5'-untranslated region(5'-UTR) of ENG c.1-127 C＞T was detected in the proband and the 2 suspected individuals,which did not exist in other family members.Based on the clinical and genetic findings,the 2 clinically suspected individuals were diagnosed as HHT.Conclusion:There is great variability of the clinical manifestations among HHT patients.ENG c.1127 C＞T mutation is the possible pathogenic variant of the HHT family.A combination of clinical and genetic diagnosis could improve the diagnosis and treatment of HHT.

OBJECTIVE: To investigate the clinical manifestation, treatment and prognosis of extramedullary plasmacytoma(EMP) in the upper airway, and to improve the diagnosis and outcome of EMP treatment. METHOD: Clinical data of 26 EMP cases were reviewed retrospectively, and then compared with multiple myeloma(MM) patients presenting with lesions in upper airway. RESULT: Of 26 cases, 9 cases with the tumors occurred in nasal cavities, 7 in nasal sinuses, 6 in pharyngeal, 4 in throat, mainly manifesting with local masses and relevant symptoms. The manifestations of clinical, endoscopy findings and pathologic results in EMP patients were not distinguishable from the lesions of MM patients, while MM patients often accompanied by other findings, such as anemia and bone damage. Involvement of neck lymph nodes was more common in MM patients than in EMP patients. Ten patients were treated with surgery, and 16 patients with surgery and radiotherapy. Of the seven EMP patients with involvement of neck lymph nodes, four patients received additional chemotherapy besides surgery and radiotherapy, and no local relapse and MM happened in them, while of the three patients only received surgery and radiotherapy, one local relapse were found and one progressed to MM. CONCLUSION The diagnosis of EMPs mainly depends on pathological results. The judgment of pathologists and application of molecular biology technology are vital for the diagnosis of EMP in upper airway, and MM must be excluded very carefully in the diagnosis of EMP. Surgery combined with radiotherapy is the main treatment for EMP in the upper airway, and the prognosis is good but the follow-up should be taken. Besides surgery and radiotherapy, chemotherapy is beneficial for the EMP patients accompanied with lesions in neck lymph nodes.
Adult ; Aged ; Female ; Humans ; Lymph Nodes ; pathology ; Male ; Middle Aged ; Multiple Myeloma ; diagnosis ; pathology ; therapy ; Nasal Cavity ; pathology ; Plasmacytoma ; diagnosis ; pathology ; therapy ; Prognosis ; Respiratory Tract Neoplasms ; diagnosis ; pathology ; therapy ; Retrospective Studies ; Young Adult

Objective:To investigate the survival benefit of radiotherapy on the basis of systemic treatment for stage ⅣB esophageal squamous cell carcinoma (ESCC).Methods:Based on inclusion and exclusion criteria, we collected the treatment information of 298 patients with newly diagnosed stage ⅣB ESCC admitted to Affiliated Cancer Hospital of Zhengzhou University from January 2016 to February 2021. All patients were divided into two groups based on treatment: early radiotherapy intervention group (CRT group, n=197) and salvage radiotherapy intervention or no intervention group (CT group, n=101). Propensity score matching (PSM) was used to balance baseline characteristics between two groups. Kaplan-Meier method was used to calculate the survival rate and log-rank was used to test the difference. Cox model was used to analyze the multivariate prognosis. Results:In the CRT and CT groups, the objective response rate (ORR) and disease control rate (DCR) were 52.8% vs. 31.5%( P=0.006) and 98.9% vs. 85.4%( P=0.001) respectively, and the 1-, 2- and 3-year survival rates were 74.2% vs. 52.8%、31.5% vs. 10.1% and 15.7% vs. 2.2%, respectively. Median progression-free survival (PFS) was 8.5 months (95% CI: 6.7-10.3 months) vs. 4.4 months (95% CI: 3.5-5.3 months)( P<0.001). Median overall survival (OS) were 17.1 months (95% CI: 14.9-19.3 months) vs. 12.7 months (95% CI: 8.0-17.4 months)( P<0.001). The difference of adverse reactions was mainly in hematology. Conclusions:For newly diagnosed stage ⅣB patients with ESCC, radiotherapy should be combined with systemic therapy as early as possible. It yields longer PFS and OS, and effectively improves dysphagia. Adverse reactions are tolerated. Further validation is recommended in larger prospective studies.

Objective:To investigate the mechanism of dexmetomidine (DEX) in improving lung injury in septic mice.Methods:Male C57BL/6 mice were randomly assigned to the blank group (NC), sham operation group (sham), cecal ligation and puncture group (CLP), and Dex treatment group (CLP+DEX), 36 mice per group. Mice in the CLP group were intraperitoneally injected with 1 mL sterile saline 15 min before CLP, and mice in the CLP + DEX group were intraperitoneally injected with 50 μg/kg DEX 15 min before CLP. The survival rate was recorded within 24 h after CLP. The mice were sacrificed at 0, 3, 6, 12, and 24 h after CLP, and lung tissues were collected. The expression levels of cytokines (IL-6, IL-1β, TNF-α) and lncRNA-HOTAIR in the lung of mice were detected by qPCR. RAW264.7 cell were cultured in vitro, LPS (100 ng/mL) and DEX (1 μ mol/L) were used to establish a cell model for studying the mechanism of Dex, and the expression of cytokines (IL-6, IL-1β, TNF-α) and lncRNA-HOTAIR in RAW264.7 cell model were detected by qPCR. In addition, the effect of lncRNA-HOTAIR on sepsis was explored in vivo and in vitro by knockdown or overexpression of HOTAIR.Results:The survival rate of the CLP+DEX group was higher than that of the CLP group within 24 h after surgery, and the levels of IL-6, IL-1β, and TNF-α in the lungs were significantly lower than those in the CLP group at 6, 12, and 24 h after surgery ( P<0.05). In addition, the level of lncRNA HOTAIR showed that the expression level of lncRNA HOTAIR in the lungs of mice were decreased after Dex treatment, and were decreased 1.1 times ( P<0.05), 4.0 times ( P<0.01) and 3.8 times ( P<0.01) at 6, 12, and 24 h, respectively. Compared with the NC group, knockdown of HOTAIR significantly decreased the levels of IL-1β, IL-6, and TNF-α in septic mice ( P<0.05), and overexpression of HOTAIR significantly increased the levels of IL-1β, IL-6, and TNF-α in septic mice ( P<0.01). Conclusions:DEX can reduce the production of inflammatory factors in the lungs of septic mice and improve the survival rate of septic mice. The mechanism may be related to the inhibition of HOTAIR expression.

OBJECTIVE: To explore the genetic basis for a patient with Leydig cell hypoplasia. METHODS: Whole exome sequencing was used to detect genetic variants in the patient. Suspect variants were verified by PCR and Sanger sequencing of the family members. RESULTS: The patient was found to carry two novel variants, namely c.265A>T (p.Ile189Leu) and c.422T>C (p.Val141Ala), of the luteinizing hormone receptor gene (LHCGR), where were respectively inherited from her father and mother. Upon prenatal diagnosis, the fetus was found to be a heterozygous carrier of the c.265A>T (p.Ile189Leu) variant. CONCLUSION The compound heterozygous variants of c.265A>T (p.Ile189Leu) and c.422T>C (p.Val141Ala) of the LHCGR gene probably underlie the Leydig cell hypoplasia in the patient.

Objective: To understand the subjective and objective comfort evaluations of students from different age groups on desks and chairs, so as to provide reference for standardized allocation and use of desks and chairs. Methods: From January to April 2024, a total of 2 446 students were selected from 26 schools in 13 districts (counties/cities) in Shanghai, Tianjin, and Wuxi from Jiangsu Province by using cluster random method, including students in kindergartens, primary schools, junior high schools,senior high schools, colleges and universities. Standardized procedures were used to measure the height and weight of participants, and the matching desks and chairs models were selected according to the height. The subjective comfort of students on matching desks and chairs was investigated, and their objective comfort was evaluated by using a self designed questionnaire. The χ 2 test was used to analyze the differences of subjective perception and objective evaluation in comfort between different types of desks and chairs. Results: About 84.1% of the students subjectively thought that large desks and small chairs were very comfortable or relatively comfortable, followed by large desks and chairs (75.7%), and the proportion of small desks and chairs was the lowest among the three types (46.2%), and the difference was statistically significant ( χ 2=722.46, P <0.01). The reporting rates of primary school, junior high school and senior high school students who subjectively considered large desks and chairs to be very comfortable/relatively comfortable were higher than that of other types of desks and chairs, and the differences were statistically significant ( χ 2=297.49, 252.82, 343.67, P <0.01). However, there was no significant difference in the subjective comfort evaluation of different types of desks and chairs among kindergarten children ( χ 2=3.21, P >0.05), and 66.3% of the students in colleges and universities felt very comfortable/relatively comfortable when they used the matching standard desks and chairs. The objective evaluation results of the comfort for the three types of desks and chairs were consistent with the subjective evaluation, but the proportions of the objective evaluation as very comfortable/relatively comfortable were higher than that of the subjective evaluation ( χ 2=20.76- 813.47, P <0.01). Conclusions Large desks and chairs, as well as large desks with small chairs are perceived comfortable, while small desks and chairs are perceived less comfortable. It is recommended to match the large desks and chairs or large desks and small chairs that are suitable for them according to the "standard", to promote physical and mental health of students.